Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions

Abstract

Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

Molecular Signaling Regulating Endometrium–Blastocyst Crosstalk

“…These conditions may lead to defects in blastocyst implantation in the maternal uterus, resulting in implantation failure, a common cause of impaired fertility [20]. The term "implantation failure" actually implies a series of conditions in which the embryo does not implant in the maternal endometrium after both spontaneous and in vitro fertilization (IVF) [21]. A condition in which implantation failure occurs after the transfer of three or more good quality embryos is defined recurrent implantation failure (RIF) and it is only applicable to assisted reproductive technology (ART) [21,22].…”

“…The term "implantation failure" actually implies a series of conditions in which the embryo does not implant in the maternal endometrium after both spontaneous and in vitro fertilization (IVF) [21]. A condition in which implantation failure occurs after the transfer of three or more good quality embryos is defined recurrent implantation failure (RIF) and it is only applicable to assisted reproductive technology (ART) [21,22]. According to ASRM and ESHRE definitions, RIF is considered a distinct pathological condition from recurrent pregnancy loss [21,23,24].…”

Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

“…Abnormal embryo implantation and implantation failure are major causes of infertility and early pregnancy loss, which is linked to other pregnancy complications [8–12]. Attainment of human endometrial receptivity occurs in the mid-secretory phase (MS) after sufficient time and concentration of progesterone exposure as seen in other placental mammals [13–18].…”

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review

“…Maternal age, lifestyle (eg, smoking, stress, and environmental contaminants), obesity, parental and embryonic genetic disorders, anatomical abnormalities, acquired and hereditary thrombophilia, autoimmune conditions, and factors related to ART are among the possible causes of RIF. Although no consensus on the correct approach for investigating and treating these couples has been reached, immunological causes are consistently listed among the possible causes of embryonic implantation failure 1 …”

“…Improvements in vitrification protocols and pre‐implantation genetic diagnosis have allowed researchers to gain a better understanding of one of the two important factors in this process, that is, the embryo 2‐5 . However, even with the knowledge obtained, cases of RIF, a challenging and very frustrating condition for all involved in efforts to achieve and maintain pregnancy, including medical staff and patients, are still present in the routine of reproductive medicine clinics 1 …”